Related Experiment Video
Updated: Nov 8, 2025
Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation
Published on: July 20, 2022
Atrial fibrillation and left atrial size and function: a Mendelian randomization study
Yordi J van de Vegte1, Joylene E Siland1, Michiel Rienstra1
1Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
Insights
Atrial fibrillation (AF) may cause enlarged left atria (LA) and reduced LA function. Genetic analysis suggests AF increases LA size and decreases ejection fraction, with a specific gene variant playing a key role.
Area of Science:
- Cardiology
- Genetics
- Biomedical Imaging
Background:
- Enlarged left atria (LA) are common in atrial fibrillation (AF) patients.
- The causal relationship between AF and LA size/function remains debated.
- Prior studies suggest a bidirectional relationship between AF and LA remodeling.
Purpose of the Study:
- To investigate the causal association between atrial fibrillation (AF) and left atrial (LA) size and function.
- To determine if genetic predisposition to AF influences LA dimensions and contractility.
- To identify genetic variants contributing to the AF-LA relationship.
Main Methods:
- Utilized UK Biobank data with cardiovascular magnetic resonance imaging.
- Measured LA maximal volume, minimal volume, stroke volume, and ejection fraction, indexed to body surface area (BSA).
- Performed two-sample Mendelian randomization analyses using 84 AF-associated genetic variants in individuals without prevalent AF.
Main Results:
- Genetically predicted AF showed a causal effect on BSA-indexed LA maximal volume, LA minimal volume, and LA ejection fraction.
- No significant causal association was found between AF and LA stroke volume.
- Exclusion of rs67249485 (near PITX2) attenuated the observed causal associations, highlighting its role.
Conclusions:
- Atrial fibrillation causally increases left atrial size.
- Atrial fibrillation causally decreases left atrial ejection fraction.
- The rs67249485 variant near the PITX2 gene is a significant contributor to the AF-associated changes in LA size and function.
Abstract:
Atrial fibrillation (AF) patients have enlarged left atria (LA), but prior studies suggested enlarged atria as both cause and consequence of AF. The aim of this study is to investigate the causal association between AF and LA size and function. In the UK Biobank, all individuals with contoured cardiovascular magnetic resonance data were selected. LA maximal volume (LA max), LA minimal volume (LA min), LA stroke volume and LA ejection fraction were measured and indexed to body surface area (BSA). Two-sample Mendelian randomization analyses were performed using 84 of the known genetic variants associated with AF to assess the association with all LA size and function in individuals without prevalent AF. A total of 4274 individuals (mean age 62.0 ± 7.5 years, 53.2% women) were included. Mendelian randomization analyses estimated a causal effect between genetically determined AF and BSA-indexed LA max, LA min, and LA ejection fraction, but not between AF and LA stroke volume. Leave-one-out analyses showed that the causal associations were attenuated after exclusion of rs67249485, located near PITX2 gene. Our results suggest that AF causally increases LA size and decreases LA ejection fraction. The AF risk allele of rs67249485, located near the PITX2 gene, contributes strongly to these associations.
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